TY - JOUR TI - Characterization of human translesion DNA synthesis across a UV-induced DNA lesion AU - Hedglin, Mark AU - Pandey, Binod AU - Benkovic, Stephen J A2 - Botchan, Michael R VL - 5 PY - 2016 DA - 2016/10/22 SP - e19788 C1 - eLife 2016;5:e19788 DO - 10.7554/eLife.19788 UR - https://doi.org/10.7554/eLife.19788 AB - Translesion DNA synthesis (TLS) during S-phase uses specialized TLS DNA polymerases to replicate a DNA lesion, allowing stringent DNA synthesis to resume beyond the offending damage. Human TLS involves the conjugation of ubiquitin to PCNA clamps encircling damaged DNA and the role of this post-translational modification is under scrutiny. A widely-accepted model purports that ubiquitinated PCNA recruits TLS polymerases such as pol η to sites of DNA damage where they may also displace a blocked replicative polymerase. We provide extensive quantitative evidence that the binding of pol η to PCNA and the ensuing TLS are both independent of PCNA ubiquitination. Rather, the unique properties of pols η and δ are attuned to promote an efficient and passive exchange of polymerases during TLS on the lagging strand. KW - DNA damage tolerance KW - translesion DNA Synthesis KW - polymerase switching KW - PCNA monoubiquitination KW - DNA polymerase eta KW - DNA polymerase delta JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -